Effects of the New Aldose Reductase Inhibitor Benzofuroxane Derivative BF-5m on High Glucose Induced Prolongation of Cardiac QT Interval and Increase of Coronary Perfusion Pressure
JOURNAL OF DIABETES RESEARCH(2016)
摘要
This study investigated the effects of the new aldose reductase inhibitor benzofuroxane derivative 5(6)-(benzo[d]thiazol-2-ylmethoxy)benzofuroxane (BF-5m) on the prolongation of cardiac QT interval and increase of coronary perfusion pressure (CPP) in isolated, high glucose (33.3 mM D-glucose) perfused rat hearts. BF-5m was dissolved in theKrebs solution at a final concentration of 0.01 mu M, 0.05 mu M, and 0.1 mu M. 33.3 mM D-glucose caused a prolongation of the QT interval and increase of CPP up to values of 190 +/- 12ms and 110 +/- 8 mm Hg with respect to the values of hearts perfused with standard Krebs solution (11.1 mM D-glucose). The QT prolongation was reduced by 10%, 32%, and 41%, respectively, for the concentration of BF-5m 0.01 mu M, 0.05 mu M, and 0.1 mu M. Similarly, the CPP was reduced by 20% for BF-5m 0.05 mu M and by 32% for BF-5m 0.1 mu M. BF-5m also increased the expression levels of sirtuin 1, MnSOD, eNOS, and FOXO-1, into the heart. The beneficial actions of BF-5m were partly abolished by the pretreatment of the rats with the inhibitor of the sirtuin 1 activity EX527 (10mg/kg/day/7 days i.p.) prior to perfusion of the hearts with high glucose + BF-5m (0.1 mu M). Therefore, BF-5m supplies cardioprotection from the high glucose induced QT prolongation and increase of CPP.
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